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Inflammopharmacology

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16.02.2024 | Original Article

Association of statin use with osteoporosis risk: a drug-targeted Mendelian randomization study

verfasst von: Zhaozhou Ren, Long Zhou

Erschienen in: Inflammopharmacology | Ausgabe 2/2024

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Abstract

Background

Hypercholesterolemia and the related inflammatory response promote the development of osteoporosis, but whether targeted interventions are protective against this bone metabolic disease remains unknown. The aim of this study was to investigate the association between the use of statins (one well-recognized cholesterol-lowering drug with anti-inflammatory properties) and the risk of osteoporosis using a drug-targeted Mendelian randomization (MR) approach.

Methods

Instrumental variables predicting three cholesterol-lowering target genes (including HGMCR) and the cholesterol effectors mediated by these genes (i.e., total cholesterol, LDL cholesterol, and non-HDL cholesterol) were extracted from expression quantitative trait loci and genome-wide association studies. Inverse variance-weighted (IVW), summary data-based MR (SMR), multivariate MR, and colocalization analysis were used to determine the association of the interventions represented by these instrumental variables with heel bone mineral density (one diagnostic indicator of osteoporosis).

Results

The IVW reported that increased levels of HGMCR-mediated total cholesterol, LDL cholesterol, and non-HDL cholesterol were associated with the decreased level of heel bone mineral density (P = 4.086e−10, P = 1.487e−09, P = 1.967e−09). The colocalization analysis supported the relationship between HGMCR-mediated non-HDL cholesterol and heel bone mineral density. The SMR reported that higher expression of HGMCR was associated with the decreased level of this osteoporosis indicator (P = 0.036). The multivariate MR further confirmed the role of HGMCR in the correlation between cholesterol traits and heel bone mineral density, and also reported that estrogen played a mediating role in the above correlations.

Conclusion

These evidence supported a protective effect of HMGCR-mediated non-HDL cholesterol reduction or statin use against osteoporosis.

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Titel: Association of statin use with osteoporosis risk: a drug-targeted Mendelian randomization study
verfasst von: Zhaozhou Ren
Long Zhou
Publikationsdatum: 16.02.2024
Verlag: Springer International Publishing
Erschienen in: Inflammopharmacology / Ausgabe 2/2024
Print ISSN: 0925-4692
Elektronische ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-024-01441-y

Springer Medizin

Abstract

Background

Methods

Results

Conclusion

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